Correlation between histone lysine methylation and developmental changes at the chicken beta-globin locus.

Methylation of histones at specific residues plays an important role in transcriptional regulation. Chromatin immunoprecipitation of dimethylated lysine 9 on histone H3 across 53 kilobases of the chicken beta-globin locus during erythropoiesis shows an almost complete anticorrelation between regions of elevated lysine 9 methylation and acetylation. Lysine 9 is methylated most over constitutive condensed chromatin and developmentally inactive globin genes. In contrast, lysine 4 methylation of histone H3 correlates with H3 acetylation. These results lead us to propose a mechanism by which the insulator in the beta-globin locus can protect the globin genes from being silenced by adjacent condensed chromatin.

Prospective matching of alcoholic clients to cognitive-behavioral or interactional group therapy.

OBJECTIVE: In earlier work, client sociopathy and global psychopathology were effective variables for treatment matching: clients low on both sociopathy and severity of psychopathology were likely to benefit from interactional group therapy, whereas those scoring high on either of these dimensions benefited more from a coping skills intervention. The present study assessed whether outcomes improve further when clients are assigned to group treatments prospectively based on a matching strategy derived from the previous findings. METHOD: All participants (N = 250, 66% men) met criteria for alcohol dependence or abuse. About half were prospectively assigned to either cognitive-behavioral (CB) coping skills training or interactional therapy, those with higher levels of psychiatric severity or sociopathy were given CB and those who were low on both dimensions were given interactional therapy. The other half were randomly assigned to those treatments, replicating the procedure of the earlier study. Outcome data were collected at the conclusion of treatment and at 3-month intervals for 1 year following. RESULTS: Prospective matching of clients to treatment did not produce superior drinking outcomes compared to random treatment assignment. Randomly assigned clients were more likely to be abstinent at the end of treatment, but this effect disappeared at later follow-ups. Prospectively matched clients had fewer negative consequences of drinking than did those assigned randomly (unmatched). Neither sociopathy nor psychiatric severity was particularly effective for matching. CONCLUSIONS: The matching effects from our previous study were not replicated. Nevertheless, prospective matching did reduce the negative consequences of drinking, consistent with our previous results.

Transitions in histone acetylation reveal boundaries of three separately regulated neighboring loci.

We have studied developmentally regulated patterns of histone acetylation at high resolution across approximately 54 kb of DNA containing three independently regulated but neighboring genetic loci. These include a folate receptor gene, a 16 kb condensed chromatin region, the chicken beta-globin domain and an adjacent olfactory receptor gene. Within these regions the relative levels of acetylation appear to fall into three classes. The condensed chromatin region maintains the lowest acetylation at every developmental stage. Genes that are inactive show similarly low levels, but activation results in a dramatic increase in acetylation. The highest levels of acetylation are seen at regulatory sites upstream of the genes. These patterns imply the action of more than one class of acetylation. Notably, there is a very strong constitutive focus of hyperacetylation at the 5' insulator element separating the globin locus from the folate receptor region, which suggests that this insulator element may harbor a high concentration of histone acetylases.

Reactivity to alcohol-related stimuli in the laboratory and in the field: predictors of craving in treated alcoholics.

AIMS: (1) To search for predictors of alcohol craving in treated alcoholics; (2) to evaluate the relationship between craving and drinking immediately after treatment. DESIGN: Alcoholic patients in treatment underwent cue-reactivity trails in the laboratory and then recorded craving in the field using hand-held computers. Laboratory craving was correlated with craving in the field, and moods and situations recorded in the field were correlated with contemporaneous craving ratings using a multi-level correlational design. SETTING: A VA Medical Center substance abuse treatment program provided the treatment and laboratory settings. The patients' home environment was the field setting. PARTICIPANTS: Male alcohol-dependent veterans (N = 26) treated in a VA inpatient or intensive outpatient program. INTERVENTION: Participants underwent two cue-reactivity laboratory sessions prior to discharge to measure craving. Following discharge, participants recorded drinking and cravings eight times per day for 21 consecutive days. MEASUREMENTS: Craving ratings in the laboratory and multiple recordings per day of surroundings, craving and mood state in the field. FINDINGS: Desire to drink in the laboratory accounted for 8-10% of the variance in later drinking and urges to drink recorded in the field--a modest correlation. Frequency of positive urges in the field was significantly correlated with drinking frequency. Those who reported urges in the field had greater alcohol dependence and higher trait anger and anxiety scores than non-reporters. CONCLUSIONS: Craving is related to drinking immediately following treatment, and is most likely in those who have more severe dependence and greater mood disturbance. These individuals may benefit most from interventions for coping with cravings after treatment.

Inducing craving for alcohol in the laboratory.

Research on the mechanisms of craving often involves inducing craving in subjects in controlled settings. This article describes techniques that have been used to induce craving for alcohol, including (1) exposing subjects to actual alcoholic beverages, (2) exposing subjects to visual representations of alcoholic beverages, (3) manipulating the subjects' mood states, and (4) controlling environmental settings. The intensity of craving can be rated by the subjects themselves or can be assessed by clinicians through behavioral observations or the measurement of certain physiological responses. Success in inducing craving in the laboratory, however, has been inconsistent. Ultimately, researchers may need to monitor subjects' craving responses in actual environmental settings.

A dental fears typology of oral surgery patients: matching patients to anxiety interventions.

Two studies are described in which dental patients were administered the Dental Fear Survey (DFS) and then received 1 of 5 anxiety reduction interventions to prepare them for extraction of 3rd-molar teeth. Interventions included standard clinic treatment, oral premedication, and several relaxation-based procedures. Dependent variables were self-reported and observer-rated distress. In the 1st study (N = 231), cluster analyses of the DFS subscales revealed that patients could be subtyped as low-fear, high-fear, or cue-anxious patients who admitted fear only in response to specific stimuli. Dental fear subtypes were distinguishable by situational cognitions reported, and fear subtype interacted with anxiety intervention to predict distress. These results were replicated in the 2nd study (N = 150). The results are seen as supportive of a multidimensional view of dental anxiety.

Ecological momentary assessment (EMA) with treated alcoholics: methodological problems and potential solutions.

Ecological Momentary Assessment, a methodology by which information can be obtained about phenomena as they occur in a person's natural environment, was used to assess the antecedents to relapse in treated alcohol abusers. Alcoholic participants (N = 27) were asked to record their urge to drink alcohol and their mood state, situation, and alcohol use on 5- x 7-in. record cards in response to 8 random prompts per day for 21 consecutive days after discharge from a Veterans Affairs inpatient treatment center. The purpose of the research was to determine the extent to which drinking urges occurred in the patient's home environment after treatment and to identify the mood states and alcohol-related stimuli associated with urges. Field recordings were prompted by a programmable wrist watch. Results suggested that compliance with procedures was excellent and that the occurrence of drinking and of drinking urges was relatively rare. However, significant methodological problems were brought to light that may have compromised the results. These problems are presented and potential solutions are proposed.

5-Azadeoxycytidine-induced chromatin remodeling of the inactive X-linked HPRT gene promoter occurs prior to transcription factor binding and gene reactivation.

During the process of 5-aza-2'-deoxycytidine (5aCdr)-induced reactivation of the X-linked human hypoxanthine phosphoribosyltransferase (HPRT) gene on the inactive X chromosome, acquisition of a nuclease-sensitive chromatin conformation in the 5' region occurs before the appearance of HPRT mRNA. In vivo footprinting experiments reported here show that the 5aCdr-induced change in HPRT chromatin structure precedes the appearance of three footprints in the immediate 5' flanking region that are characteristic of the active HPRT allele. These and other data suggest the following sequence of events that lead to the reactivation of the HPRT gene after 5aCdr treatment: (a) hemi-demethylation of the promoter, (b) an "opening" of chromatin structure detectable as increased nuclease sensitivity, (c) transcription factor binding to the promoter, (d) assembly of the transcription complex, and (e) synthesis of HPRT RNA. This sequence of events supports the view that inactive X-linked genes are silenced by a repressive chromatin structure that prevents the binding of transcriptional activators to the promoter.

Alcohol cue reactivity, negative-mood reactivity, and relapse in treated alcoholic men.

Relapsed alcoholic individuals frequently report that negative emotional states trigger their return to drinking. A parametric laboratory study was conducted to assess the separate and combined effects of exposure to alcohol-related stimuli and induced negative moods in abstinent alcoholic persons. The authors also sought to determine if reactivity to alcohol cues or reactivity to negative mood induction predicted relapse soon after treatment. Men with alcoholism (N = 50) undergoing inpatient treatment participated in a guided imagery procedure designed to induce negative moods and were then exposed to either their favorite alcoholic beverage or to spring water. Results indicated that both alcoholic beverage presentation and negative affect imagery led to increased subjective reporting of desire to drink. These effects were additive but not multiplicative (i.e., the interaction of mood state with beverage type was not significant). Reported urge to drink during the trial that combined negative mood imagery with alcoholic beverage exposure predicted time to relapse after inpatient discharge.

In vivo footprinting and high-resolution methylation analysis of the mouse hypoxanthine phosphoribosyltransferase gene 5' region on the active and inactive X chromosomes.

To investigate potential mechanisms regulating the hypoxanthine phosphoribosyltransferase (HPRT) gene by X-chromosome inactivation, we performed in vivo footprinting and high-resolution DNA methylation analysis on the 5' region of the active and inactive mouse HPRT alleles and compared these results with those from the human HPRT gene. We found multiple footprinted sites on the active mouse HPRT allele and no footprints on the inactive allele. Comparison of the footprint patterns of the mouse and human HPRT genes demonstrated that the in vivo binding of regulatory proteins between these species is generally conserved but not identical. Detailed nucleotide sequence comparison of footprinted regions in the mouse and human genes revealed a novel 9-bp sequence associated with transcription factor binding near the transcription sites of both genes, suggesting the identification of a new conserved initiator element. Ligation-mediated PCR genomic sequencing showed that all CpG dinucleotides examined on the active allele are unmethylated, while the majority of CpGs on the inactive allele are methylated and interspersed with a few hypomethylated sites. This pattern of methylation on the inactive mouse allele is notably different from the unusual methylation pattern of the inactive human gene, which exhibited strong hypomethylation specifically at GC boxes. These studies, in conjunction with other genomic sequencing studies of X-linked genes, demonstrate that (i) the active alleles are essentially unmethylated, (ii) the inactive alleles are hypermethylated, and (iii) the high-resolution methylation patterns of the hypermethylated inactive alleles are not strictly conserved. There is no obvious correlation between the pattern of methylated sites on the inactive alleles and the pattern of binding sites for transcription factors on the active alleles. These results are discussed in relationship to potential mechanisms of transcriptional regulation by X-chromosome inactivation.

Presurgical satisfaction with facial appearance in orthognathic surgery patients.

Orthognathic surgery and orthodontic therapy are most often performed to improve the patient's appearance. However, not all patients are satisfied with the result though the procedure may be considered successful by the orthodontist and the maxillofacial surgeon. It has been suggested that the patient's satisfaction with his or her facial appearance before the surgery can predict later satisfaction with orthognathic procedures. The present study examined the role of several potential predictor variables in satisfaction with facial appearance before orthognathic treatment. The variables, identified in previous research, included severity of facial disharmony, self-concept, psychological distress, gender, age, and socioeconomic status. Questionnaires were gathered from 54 patients in 10 orthodontic practices in Connecticut and New York. Contrary to expectations, gender, age and socioeconomic status failed to predict patients' presurgical satisfaction with appearance. Self-concept, psychological distress, and orthodontists' ratings of total facial appearance (from a lateral view) were bivariate predictors of satisfaction. When all variables were analyzed with a multiple regression analysis, however, only self-concept emerged as a significant independent predictor of satisfaction with appearance. This accounted for 15% of the variance in satisfaction. Orthodontists' ratings of facial views, considered here objective measures of disharmony, were predictive neither of satisfaction with appearance nor of self-concept. It is suggested that self-concept may be a predictor of postsurgical as well as presurgical satisfaction with appearance and that self-concept itself may be unaffected by severity of facial disharmony, at least in young adults. Orthodontists may need to pay special attention to those patients with poor self-concept, because these patients may be more likely to report unsatisfactory surgical outcomes.

Self-efficacy as a component of active coping: effects on cardiovascular reactivity.

Active coping remains a poorly understood construct in cardiovascular reactivity testing. We have shown that active coping comprises two independent effects: the enhanced control and the effort of exercising control. The present study tested the proposition that, with effort left unconstrained, increased self-efficacy will increase cardiovascular response. Forty women were assigned to low or high self-efficacy conditions; self-efficacy was manipulated using false feedback. Subjects then engaged in a video game shape-matching task, while blood pressure and heart rate were monitored. SBP and DBP changes were smaller in the low self-efficacy group, as predicted: 17.9 versus 25.2 mmHG for SBP (p < 0.05); and 8.7 versus 13.0 mmHG for DBP (p = 0.07). Heart rate was similar for the two conditions. We conclude that self-efficacy for a task may be an integral part of the active coping process, indirectly affecting the blood pressure response by acting on the effort involved in the coping response.

A model of pain and anxiety associated with acute stressors: distress in dental procedures.

Many acute stressful experiences are not inherently very harmful, yet are associated with great pain and anxiety. The characteristics and experiences that the person brings to the situation are more important than any objective characteristics of the experience itself in determining how aversive the experience will be. Dental procedures are excellent examples of this type of stressor. Drawing primarily on the literature related to dental procedures, the present article discusses the nature of pain and anxiety in the face of an acute stressor, and presents the dispositional and situational factors that contribute to the perception of an acute stressor as aversive. A model is presented illustrating how the various factors interact. It is argued that, in addition to being descriptive, the model is also prescriptive of measures that may be taken to ameliorate the distress of persons subjected to acute stressors like dental procedures.

Craniomaxillofacial trauma in the elderly.

PURPOSE: Limited data are currently available regarding the nature of craniomaxillofacial fractures in the geriatric population. This retrospective study reviews 109 hospital records dating from 1981 to mid-1993. The goal of this study was to provide details relevant to these types of injuries. RESULTS: Most patients were injured in motor vehicle accidents (MVA) or fall-related episodes. Females sustained 43.9% of the fractures while males sustained 56.1%. In females, falls were the most common cause of fractures, while in males MVAs caused the majority of fractures (P < .01). Most fractures were found in the upper midface region (60.3%) and the mandible (27.5%). MVAs and falls were responsible for 82.7% of all mandibular fractures. The majority of fractures were treated nonsurgically (49.5%); however, 37.6% were treated with open reduction and internal fixation. The in-hospital mortality rate was 11.1%, and there were three postoperative complications. CONCLUSION: The geriatric craniomaxillofacial trauma patient is readily treatable with both aggressive surgical measures and more conservative approaches. Elderly patients often have an underlying medical condition that may subsequently alter the patient's treatment. The findings of this study also suggest that more preventive measures and methods of minimizing mortality and morbidity need to be implemented.

Preparation for oral surgery: evaluating elements of coping.

Third-molar extraction patients (N = 231) underwent one of five preparatory interventions offering different levels of relaxation, control, and self-efficacy to evaluate the relative importance of each of these elements of coping in the context of an acute stressor. Prior to surgery subjects completed measures of monitoring and blunting. Results indicated that relaxation, perceived control, and self-efficacy were each significant, and roughly equivalent, contributors to coping, and operated in an additive way. Intervention type, and the interaction of intervention type with blunting score, significantly predicted distress prior to and during surgery. It was concluded that no single element is crucial to effective coping and that interventions that provide more coping elements are generally superior. Additionally, the interaction of coping style with intervention is as strong a contributor to coping outcome as the other factors. Those who prefer to distract themselves may benefit most from interventions that require the least possible personal investment of effort and attention.

Multidimensional causal model of dental caries development in low-income preschool children.

Despite the decline in the incidence of dental caries in the United States over the past several years, the condition remains a significant problem for the nation's poor children. Efforts to identify the factors responsible for caries development in samples of children of low socioeconomic status have primarily focused on a limited number of variables, and those have been predominantly biological (mutans streptococci, for example). Resulting models of caries development have usually shown good sensitivity but poor specificity. They have had limited implications for treatment. In an effort to produce a comprehensive model of caries development, 184 low-income preschool children were clinically assessed for mutans streptococci and for decayed, missing, or filled surfaces of deciduous teeth twice, first at age 4 years (baseline) and again a year later (year 1 assessment). As the clinical assessments were being done, caretakers were being interviewed to obtain data from five domains: demographics, social status, dental health behaviors, cognitive factors such as self-efficacy (self-confidence) and controllability, and perceived life stress. Data were analyzed using a structural equations modeling approach in which variables from all domains, plus baseline decayed missing and filled surfaces and baseline mutants, were used together to create a model of caries development in the year 1 assessment. Results confirmed earlier work that suggested that caries development at a 1-year followup was strongly dependent on earlier caries development. Early caries development in this sample was determined in part by mutans levels and by dental health behaviors. These behaviors themselves were accounted for partly by a cognitive factor. The results support the advantages of employing multidimensional models and provide some direction for intervention to reduce caries incidence.

Self-efficacy as a moderator of perceived control effects on cardiovascular reactivity: is enhanced control always beneficial?

We have found that enhanced control has an attenuating effect on cardiovascular reactivity when effort of responding is maintained constant; however, not all individuals will react to increased control in the same manner. In the present study, 40 subjects engaged in a mental arithmetic task under high control (self-paced) and low control (externally paced) conditions. Subjects' self-efficacy concerning this task was assessed. As expected, significant main effects were found for control condition, with high control producing smaller blood pressure and heart rate changes than low control (11.4 vs. 20.4 mm Hg (systolic blood pressure), 4.4 vs. 11.4 mm Hg (diastolic blood pressure), and 6.2 vs. 7.9 beats per minute (heart rate)). No main effects were found for self-efficacy. However, the interaction between control and self-efficacy was significant for systolic blood pressure and heart rate and marginally significant for diastolic blood pressure; post hoc tests showed that this was due to the effect of self-efficacy classification under high control conditions; subjects with low self-efficacy for the mental arithmetic task evidenced cardiovascular changes that were significantly greater than those of the high self-efficacy group (8.0 vs. 14.8 mm Hg (systolic blood pressure), 2.7 vs. 6.1 mm Hg (diastolic blood pressure), and 5.2 vs. 7.1 beats per minute (heart rate). The data suggest that the reactivity observed during active coping is due in part to the effort of responding and in part to the match between the demands of the task and certain mastery-related attributes of the individual.

The type A/type B distinction. Subtyping alcoholics according to indicators of vulnerability and severity.

Multidimensional typologies of alcoholics are reviewed, including Cloninger's neurobiological learning model, Morey and Skinner's hybrid model, and Zucker's developmental model. The more recent Type A/Type B typology proposed by Babor and colleagues is reviewed in more depth, as is a previous replication and extension by Litt and colleagues. Both the original study and the replication indicate this typology is a useful tool in classifying alcoholic inpatients into two groups and in matching alcoholics to the most suitable treatment. The present study replicates the typology using outpatient samples of male alcoholics. The resulting two clusters are very similar to those identified by the two earlier studies. As expected, the relative proportion of Type A alcoholics is higher in the outpatient samples than in the previously studied inpatient samples. Preliminary analysis of the typology's clinical efficiency suggests that the variables used to classify subjects might be appreciably reduced, thus effecting a considerable time savings in assessment. A discriminant function analysis indicates that using only 5 of the original 16 clustering variables results in a correct classification rate of almost 95%. Future research directions are addressed.

Coping with oral surgery by self-efficacy enhancement and perceptions of control.

Recent work has suggested that patients' coping could be improved in stressful dental situations if perceptions of self-efficacy and control could be enhanced. To test this hypothesis, 70 first-time third-molar extraction patients were randomly assigned to one of four surgery preparation conditions: standard preparation, oral premedication, relaxation, and a relaxation+efficacy-enhancing feed-back condition in which subjects were given false galvanic skin response (GSR) biofeedback leading them to believe that they were highly skilled at relaxing. Analyses indicated that: (1) all treatments were seen as equally credible (controlling for placebo effects); (2) a priori contrasts showed that both the relaxation-only treatment and the relaxation+efficacy-enhancement treatment were superior to the premedication and standard preparations in raising coping self-efficacy; (3) regardless of treatment condition, increase in reported coping self-efficacy was significantly correlated with pre-operative anxiety, with self-reported peri-operative distress, and with behavioral ratings of peri-operative distress; and (4) the relaxation treatments resulted in lower pre-operative anxiety than the other interventions, and linear contrasts showed significant trends in which the relaxation+efficacy-enhancing condition was superior to the relaxation-only condition, which was in turn superior to the medication condition and the standard preparation in reducing both pre-operative anxiety and behavioral ratings of peri-operative distress. It was concluded that thoughts related to self-confidence and control can be manipulated, and that these thoughts can in part determine how well a person copes in stressful dental situations.